The NHLBI is requesting competing renewal applications from the eight clinical centers and data coordinating center (DCC) currently funded as part of the Severe Asthma Research Program (SARP). These programs were awarded as a result of Request for Applications (RFA) HL-01-012, Severe Asthma Research Program (http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-01-012.html). This program provides a unique collaborative structure for clinical research studies on the mechanistic basis of severe asthma and how it differs from mild-to-moderate asthma. The group has expended extensive efforts to establish collaboration, implement protocols, and maintain high quality data bases suitable for a collaborative clinical research program. Pending successful peer-review, the program is offered this opportunity to work together for one additional 5 year grant cycle in order to take maximum advantage of this experience. This re-competition will continue to focus on the pathophysiology of severe asthma and how it differs from mild-to-moderate asthma for a one-time renewal cycle. After that point, the NHLBI will determine the feasibility and need for maintaining a collaborative research program in severe asthma and, if appropriate, will issue a new request for applications as an unlimited competition.

Mechanism of Support

The limited competition for SARP uses the NIH R01 award mechanism. Details of the responsibilities, relationships, and governance of a program funded under this Notice will be the same as in the current terms and conditions of the award.

The total project period for an application submitted in response to this Notice may not exceed five (5) years. This program will end as of June 30, 2011. No renewal of the program will occur. The anticipated award date is July 1, 2006.

Funds Available

The NHLBI intends to commit approximately $28 million in total costs over the course of the 5 year program. An applicant may request a project period of 5 years and a budget for direct costs of up to $400,000 per year. Although the financial plans of the NHLBI provide support for this program, awards pursuant to this Notice are contingent upon the availability of funds.

Submitting an Application

Applications must be prepared using the PHS 398 research grant application instructions and forms. Applications must have a DUN and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier when applying for federal grants or cooperative agreements. The DUNS number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/. The DUNS number should be entered on line 11 of the face page of the PHS 398 form. The PHS 398 document is available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. For further assistance contact Grants Info, Telephone (301) 435-0714, E-mail: GrantsInfo@nih.gov.

Supplemental Instructions: Only competing renewal applications, which were funded as part of RFA HL-01-012, Programs of Summer Institute for Training in Biostatistics, will be considered.

For every application, Item 2 on the Face Page should be checked “Yes”; after “Number:” enter “NOT-HL-05-125” and after “Title:” enter “Competing Applications for SARP.”

Additional Material to Include in the Application To promote development of a collaborative program among the award recipients, the issues discussed below need to be addressed in each application for the Research Program. This material is in addition to the submission of a research plan, as described in the section entitled Research Scope. Willingness to participate in the Severe Asthma Research Program. Applicants should provide a written statement describing their general support of collaborative research and interaction with other institutions participating in the Program and specifically state their willingness to implement common guidelines developed by the Steering Committee as well as share patients, samples and data when appropriate as determined by the Steering Committee.

Sending an Application to the NIH: Submit a signed, typewritten original of the application, including the Checklist, and three signed photocopies in one package to:

Application Processing: Applications must be received on or before the application receipt date listed in the heading of this Notice. If an application is received after that date, it will be returned to the applicant without review.

Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review date within 8 weeks.

Peer Review Process

Applications that are complete will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NHLBI in accordance with the process stated below. Each application will:

Receive a written critique and a priority score

Receive a second level review by the National Heart, Lung, and Blood Advisory Council

Review Criteria

The proposed Severe Asthma Research program is intended to elucidate the pathophysiology of severe asthma. In the written comments, reviewers will be asked to discuss the following aspects of your application in order to judge the likelihood that the proposed research program will have a substantial impact on the realization of this goal:

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

Additional Review Criteria

In addition to the above criteria, your application will also be reviewed with respect to the following:

Study population: Applicants must have the ability to enroll over the 5 years at least 25-50 patients with severe asthma. The pool of potential study participants in the Severe Asthma Research Program should consist of appropriate gender and minority representation. The application must include a description of the pool of potential study participants--the age range, ethnic/racial distribution, estimated distribution of patients with different levels of asthma severity, and recruitment source. Access to at least 25-50 patients for research studies over the 5 year period is expected, but it is not anticipated that all patients will be enrolled in research studies at any one time, and it is possible that an individual patient may be enrolled in more than one study. Patient access may be accomplished by establishing links with other groups besides the applicant's institution. There must be a well described plan to link the individual institutions with community health care providers such as HMOs, asthma clinics, or private practice physicians to ensure adequate numbers patients.

Collaboration: Applicants must demonstrate a significant role in the collaborative nature of the program during the previous 5 year grant cycle in terms of enrollment of severe asthma patients, sharing of samples and data, where appropriate, development of common enrollment and research protocols, research synergy with other centers where appropriate. Ongoing commitment to program cooperation and collaboration should be demonstrated for the second 5 year cycle.

Institutional Commitment and Resources:

Adequacy and availability of any necessary institutional facilities.

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under Section F of the PHS Form 398 research grant application instructions will be assessed.

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s)to be used in the proposed research. Applications that do not provide this information will be returned without review.

NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from 1) currently funded NIH research projects or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002 . The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.